Project Summary Pancreatitis is a significant public health problem, accounting for over $2 Billion of health care costs annually. Approximately one third of patients with acute pancreatitis will go on to have recurrent pancreatitis. Of those, about 10% will progress to chronic pancreatitis, a painful disease with an increased risk of both diabetes and pancreatic cancer. More than 20% of people with just one episode of pancreatitis will develop diabetes. Currently treatment for pancreatitis is palliative as there is no specific treatment available. The pancreas has two parts: the exocrine part where digestive enzymes are made and the endocrine part where insulin is made. Pancreatitis occurs when digestive enzymes are activated and released into the pancreatic tissue rather than into the intestine. In the tissue they initiate pancreatitis through their digestive activity. We have identified a new drug, SBP-101, which is relatively specific for the pancreas and has been shown in pilot studies to decrease the severity of acute pancreatitis and the associated systemic inflammation. Our results suggest that administration of a single dose may be effective as a specific treatment for pancreatitis. We will evaluate 101 using in vivo models to test the hypothesis that treatment with SBP-101 lessens the injury caused by activated digestive enzymes in the tissue resulting in attenuation of pancreatitis. Our experiments are designed to determine the effects of SBP-101 on the exocrine pancreas, secretion of enzymes into the blood stream, systemic inflammation, production of pro-inflammatory cytokines and cell viability. The in vivo experiments are specifically designed to determine the effect of SBP-101 in the setting of both mild to moderate acute pancreatitis and severe acute pancreatitis. The body of work resulting from this project will serve as a proof of concept that SBP-101 is a candidate for clinical trials to test the efficacy of SBP-101 in the treatment of pancreatitis. Because there are no currently available treatments, a positive result from this project will have a considerable impact on the field.